Duodenal levodopa infusion for the treatment of Parkinson's disease

Motor fluctuations are a common problem in the long-term management of Parkinson's disease (PD), resulting in disability and impaired quality of life. The relatively short serum half-life (similar to 90 min) of oral levoclopa/carbiclopa and its erratic absorption due to delayed and inconsistent gastric emptying (a non-motor feature of PD) are thought to be important factors in the development of motor fluctuations. Continuous infusion of levoclopa/carbiclopa directly into the small intestine of PD patients results in marked reduction of motor fluctuations by reducing plasma levoclopa variability by an order of magnitude over oral therapy. Previously, the use of long-term intracluodenal infusion of levoclopa/carbiclopa was limited by the relatively large volumes of infusate necessitated by the low solvency of levoclopa. The development of a micronized levoclopa (20 mg/ml) and carbiclopa (5 mg/ml) suspension utilizing a methylcellulose gel provides the high levoclopa concentration and physical and chemical stability necessary for long-term enteral therapy. Clinical evidence indicates that a marked reduction of motor fluctuations and dyskinesias can be achieved and maintained by intracluodenal administration of this suspension. This article reviews the published data describing the efficacy and safety of duodenal levoclopa, and discusses its current and potential role in meeting the needs of PD patients.